γδ T Cell Therapy Development for Systemic Lupus Erythematosus (SLE)

Based on abundant experience and high-end technologies, Creative Biolabs is confident in providing high-quality and custom development services for the exploration of γδ T cell pathogenetic and therapeutic roles in systemic lupus erythematosus (SLE).

Systemic Lupus Erythematosus Overview

SLE is a chronic autoimmune disorder whose originating pathogenesis is caused by an aberrant immune response involving multiple organs. The hallmark of SLE is the production of autoantibodies, particularly those pathogenic autoantibodies against self-nuclear antigens, such as double-stranded DNA and Sm antigen. SLE is prevailing among women leading to a series of widely clinical presentations, like arthritis, blood cell abnormality, and skin symptoms.

Endogenous nucleic acids released by apoptotic cells serve as self-antigens that activate autoreactive T lymphocytes, B lymphocytes, and stimulate the production of various cytokines. Self-antigens are recognized by dendritic cells (DCs), by which the activated DCs secrete pro-inflammatory cytokines and present self-antigen to T cells. As a consequence, T cells are activated, together with follicular DCs in the germinal center, activating B cells to produce autoantibodies. These autoantibodies react with auto-antigens forming immune complexes. These immune complexes are deposited in different tissues and organs through circulation, inducing phagocytosis, cytotoxicity, and chronic inflammation, and thereby resulting in SLE with different clinical manifestations.

Fig.1 Schematic representation of the pathogenesis of SLE. (Ferretti, 2016)

γδ T Cell Functions in Systemic Lupus Erythematosus

The human γδ T cell is a category of T lymphocytes carrying an alternative γδ T-cell receptor (γδTCR). Although only accounting for ~5% of the total T cells, γδ T cells play an important function in both innate and adaptive immune responses. Published studies reported that a remarkably lower number of γδ T cells in the peripheral blood and a much higher number of γδ T cells in chronic cutaneous lupus erythematosus lesions of SLE patients compared with the healthy individuals, suggesting that γδ T cells had a regulatory role in SLE.

Different from in other autoimmune diseases like rheumatoid arthritis, multiple sclerosis, and idiopathic bowel disease where interleukin-17 producing γδ T cells (γδ T17 cells) play a pathogenetic role in the disease development, γδ T17 cells in SLE patients are no different from those in normal controls. It is CD4+ regulatory γδ T cells and CD27+CD25 Vδ1 T cells that involve in the progression of SLE. γδ T cells in SLE patients showed an increased expression of HLA-DR, an antigen-presenting cell (APC) specific receptor, leading to enhanced APC like function and overreaction of γδ T cell. Moreover, γδ T cells provide help for B cell in autoantibody production, which also results in promoting the development of SLE.

Fig.2 Hypothetical model incorporating the immunopathogenetic role of γδ T cells in human SLE. (Bank, 2020)

γδ T Cell Therapy Development Services for SLE

γδ T cells play an extremely complex role in the pathogenesis of SLE. More specific pathogenesis of γδ T cells in SLE has yet to be elucidated and related γδ T cell immunotherapy has yet to be explored. As a recognized reliable partner, Creative Biolabs provides fully custom services for the γδ T cell-based pathogenesis investigation and immunotherapy development. Additionally, a comprehensive range of γδ T cell products and engineering services are also within our scope.

If you are interested in, please directly contact us, our seasoned scientists will offer you the most tailored solutions and support.

References

1. Ferretti, C., La Cava, A. Overview of the pathogenesis of systemic lupus erythematosus. In Systemic Lupus Erythematosus. 2016, pp: 55-62.
2. Bank, I. The Role of Gamma Delta T Cells in Autoimmune Rheumatic Diseases. Cells. 2020, 9(2): 462.